Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.


Export to Word (
Principal Investigator: Segal, David J
Institute Receiving Award University Of California At Davis
Location Davis, CA
Grant Number R21ES033460
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 17 Sep 2021 to 31 Aug 2023
DESCRIPTION (provided by applicant): ABSTRACT Our capacity for health and disease is intimately tied with the environment and the experiences to which we are exposed. Life experiences, then, can yield lasting consequences on development, behavior, and health. Those occurring during the sensitive period early in life can be especially potent. Early life adversity (ELA) is highly and universally prevalent, and accounts for increased mortality, as well as increased rates of mental and physical pathophysiology. This is manifested in the incidence of mental health disorders and chronic medical conditions well into adulthood, as well as cardiovascular disease, inflammation, obesity, and cancer. Studies suggest that 60.9% of adults reported to have experienced a minimum of one type of adverse childhood exposures (ACE), and 15.9% experienced multiple ACEs. This recent statistic underscores the sheer prevalence and far-reaching consequences of ELA on human health and behavior, as well as emphasizing the importance of studies that consider multiple contemporaneous ACEs. The association of environmental exposures (including air pollution and traumatic ELA) and epigenomic changes has been well-recognized. However, in order to inform interventions that address public health issues effectively, the tantamount question regarding the pathophysiological bases of ACEs – how they “get under the skin” via epigenome modification, and how and which of these epigenomic changes are causally or functionally relevant to the disease phenotypes observed – remains poorly understood. In this proposal, we will identify epigenetic and genetic events with robust phenotypic consequences occurring in a mouse model of ACE. We will use a unique model at UC Davis in which mice are exposed to traffic-related air pollution (TRAP) during development, representing an environmental factor known to be associated with increased risk of neurodevelopmental disorders, including cognitive impairment, psychomotor deficits, and hyperactivity. As a contemporaneous ACE, we will apply the limited bedding and nesting (LBN) paradigm of fractured caregiving, associated with several similar phenotypic outcomes. We hypothesize that the two ACEs will have additive or synergistic effects on molecular and behavioral outcomes. Complementary to these studies, we will investigate the hypothesis that changes in epigenetic information are an important physical component of how chronic adverse childhood exposures manifests consequences later in life. This project builds upon an interest in studying glucocorticoid receptor (GR) expression and regulation in the dorsal hippocampus – whether specific gene expression changes induce specific structural and functional changes has not yet been ascertained. We expect to identify distinct and functionally noteworthy epigenetic “signatures” related to these phenotypic characteristics, based on related studies. The long-term goal of this study is to identify and prioritize epigenetic events and robust phenotypes that will enable future studies in which the functional significance of specific epigenetic information can be investigated through epigenetic editing. Therefore, the data collected in this exploratory proposal will form the basis to investigate causal relevance between epigenetics and ACE-induced behavioral phenotypes.
Science Code(s)/Area of Science(s) Primary: 61 - Neurodevelopmental
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications No publications associated with this grant
Program Officer Jonathan Hollander
to Top